Macrocyclic Peptides and Depsipeptides

Macrocydic peptides and.depsipeptides (-macrocyclic peptides with amide and ester linkages) are important natural compounds. They have been synthesized in low yield from open-chain precursors by DCC treatment at high dilution (E. Schroder, 1963 M.M. Shemyakin, 

More successful are solid-phase methods in which the linear precursor is attached through a labile ester bond (e.g. o-nitrophenyl) to a polymer. 

First the protected oligopeptide is coupled with polymer-bound nitrophenol by DCC. N -Deblocking leads then to simultaneous cycliration and detachment of the product from the polymer (M. Fridkin, 1966). Recent work indicates that high dilution in liquid-phase cycli-zation is only necessary, if the cyclization reaction is sterically hindered. Working at low temperatures and moderate dilution with moderately activated add derivatives is the method of choice for the formation of macrocyclic lactams (R.F. Nutt, 1980). 

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Synthesis of macrocyclic peptides and depsipeptides with cytotoxic activity 88YZ1115. 

TE-catalyzed cyclization is not limited to the synthesis of macrocyclic peptides by catalyzing the formation of aC N bond. These enzymes are also responsible for the cyclization of NRP depsipeptide and PK lactone. Indeed, a di-domain excised from fengycin synthase was... 

Among the macrocyclic natural and synthetic drugs the cyclic peptides and cyclic depsipeptides play a central role in particular as anti-infective" and... 

Enantiomerically pure non-proteinogenic amino acids have attracted recent attention due to their antibiotic [1], antifungal [2], cytotoxic [3], and other important pharmacological properties [4]. Frequently, they also occur incorporated in natural products, such as peptides, depsipeptides, and other macrocyclic compounds. Other important applications are to serve as building blocks in asymmetric synthesis. A specifically prominent class of them are cyclic 3- and y-amino acids, the subject to which the present chapter is dedicated. 

Guidelines for the synthesis of cyclopeptides have it that pendant groups should be connected to the cyclic scaffold after ring closure. Moreover, peptide bond formation is generally preferred to ester bond formation as a means to accomplish macrocyclization of depsipeptide frameworks, and it is also well established that primary amino groups react more efficiently than secondary ones in peptide bond forming reactions i.e., secondary amides are more readily formed than tertiary ones. Retrosynthetic dissection of the only pair of secondary amide bonds in luzopeptin A-C precursor 11 leads to pentadepsipeptide 12 (Scheme 3). 

As already mentioned, the depsipeptides associate ester bonds with peptide bonds. As most of the depsipeptides of cyanobacteria are macrocyclic, this concerns lactone and lactam fimctions. Laingolide, laingolide A, madangolide and palmyrohde A are simple cyclic depsipeptides (one... 

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